Kinin and histamine stimulate Cl- secretion in gerbil middle ear epithelium: connection to otitis media

The effects of bradykinin (BK) and histamine on transepithelial ion transpo rt in primary cultures of gerbil middle ear epithelium were investigated. L ysyl-bradykinin (lys-BK) elicited a transient increase in short-circuit cur rent (I-sc) when added to apical or basolateral surfaces. Lys-BK had a larg er effect than BK or des-arg(9)-BK on both epithelial surfaces. Histamine i nduced a transient increase in I-sc. only when added to the basolateral sur face. Mepyramine, an H-1 histamine antagonist, greatly reduced the histamin e-induced I-sc. The H-2 and H-3 histamine antagonists were both ineffective for inhibiting the I-sc responses to histamine. Diphenylamine-2-carboxylat e or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, Cl- channel blockers , significantly blocked the I-sc responses to lys-BK or histamine. The Ca2-mobilizing action of lys-BK and histamine was also investigated in single middle ear epithelial cells. BK and histamine induced an increase in the in tracellular Ca2+ concentration. 1,2-Bis-(2-aminophenoxy)ethane-N,N,N',N'-te traacetic acid-acetoxymethyl ester, a calcium chelator, greatly reduced the increase in the I-sc responses to lys-BK or histamine. These data indicate that BK and histamine activate intracellular Ca2+-dependent mechanisms, le ading to apical Cl- secretion in the cultured gerbil middle ear epithelium via B-2 BK receptors and H-1 histamine receptors. (C) 1999 Published by Els evier Science B.V. All rights reserved.